Human rhinoviruses (HRV) are the leading cause of the common cold and more recently have been implicated in lower respiratory illness, in infants and children. While many respiratory viruses have been associated with asthma exacerbations, HRV are the most common trigger of asthma exacerbations and chronic obstructive pulmonary disease (COPD) in children and adults. The rates of HRV-associated acute respiratory illness medical visits in US adults are not known. Recently, a new group of HRV designated HRVC was identified that may associate with asthma and COPD exacerbations. The impact of the novel HRVC on US adults has not been established, and the association of HRVC with obstructive wheezing diseases such as asthma and COPD is unclear. We propose to define the role of HRV and the novel HRVC group in adults and children seen as outpatients or hospitalized with ARI/fever, including those with asthma or COPD exacerbation. The central hypotheses of our proposal are that HRV are commonly associated with ARI/fever in adults and children and that HRVC associate with wheezing and more severe respiratory disease. The results of the proposed research will help guide vaccine development and elucidate mechanisms of virus-induced asthma. The findings of this work may lead to new approaches to treat and prevent asthma. We propose three Specific Aims: 1) to determine the rates of HRV in adults and children who seek medical care for acute respiratory illness (ARI) or fever, 2) to determine the rates of HRV species A, B, and C that are associated with ARI/fever in adults and children seen in different clinical settings, and 3) to determine rates of HRV and HRV species associated with obstructive wheezing illness such as asthma and chronic obstructive pulmonary disease (COPD) among adults and children. This research allows us to understand the burden of HRV and HRVC in US adults and children, as well as which HRV genotypes affect certain age groups, and elucidates the relationship between severity and type of respiratory disease and viral species. This may ultimately allow for a more targeted vaccine to be developed against HRV and may shed light on certain groups, such as those with asthma or COPD, at risk for more severe HRV-associated disease. PUBLIC HEALTH RELEVANCE: Human Rhinovirus (HRV) is the leading cause of the common cold and is commonly associated with wheezing illnesses like asthma and chronic obstructive pulmonary disease (COPD). We propose to define the burden of HRV and HRV species among children and adults in a large US metropolitan area, with or without wheezing, and to investigate other host factors that may contribute to species susceptibility. This work will further our understanding of HRV epidemiology and pathogenesis and may ultimately allow for a more targeted vaccine to be developed against HRV and shed light on certain groups at risk for more severe HRV-associated disease.